Nickel compounds have been implicated as human carcinogens on the basis of several epidemiological studies. Various nickel compounds have been shown to induce tumors of diverse histologic types in several species of experimental animals. The extent of the human hazard has not been defined because (a) a reliable, rapid, and inexpensive method for screening the carcinogenic potential of the myriad of nickel compounds in the environment has not been developed; (b) the mechanism by which nickel compounds exert their carcinogenic effect is largely unknown; (c) the intermediary metabolism of other inorganic and organic carcinogens in concert with carcinogenic nickel compounds is incompletely understood. With the primary goal of elucidating these areas of concern, we propose (1) to develop and validate a tissue culture system which can act as both a screening technique and a test system for elucidating molecular mechanisms of nickel carcinogenesis. Using this system we will screen a large number of nickel compounds for carcinogenic potency; (2) to study the relationship between solubility and carcinogenicity of nickel compounds; (3) to examine the intracellular distribution of carcinogenic nickel compounds; (4) to study the early biochemical changes during nickel induced carcinogenesis in tissue culture.